IMPACT OF CO-MORBID AMYLOID PATHOLOGY ON CLINICAL PHENOTYPE OF PATIENTS WITH VASCULAR COGNITIVE DISORDERS

Abstract

Cerebrovascular disease is an important cause of cognitive impairment and dementia, and vascular cognitive disorders (VCD) are conceptually distinct from Alzheimer's disease (AD). However, cerebrovascular and amyloid pathology may be co-morbid, particularly in older patients. Amyloid-beta biomarkers can detect amyloid pathology in vivo. Our aim was to investigate the impact of co-morbid amyloid pathology on the clinical phenotype of patients with VCD. From the Amsterdam Dementia Cohort we included 218 patients with VCD who fulfilled the 2014 VASCOG criteria (66 with Major VCD and 152 with Mild VCD). As a reference group we included 120 patients with (prodromal) AD (85 with MCI and 35 with dementia due to AD). All subjects underwent a diagnostic work-up including brain MRI and lumbar puncture. We defined presence of amyloid pathology (A+) as CSF Abeta-42 <638ng/L. VCD patients were termed V+, patients in the reference group V-. This resulted in 116 A+V+, 102 A-V+, and 120 A+V- patients. We used linear regression analysis to compare MMSE scores, z-scores for neuropsychological test performance in five cognitive domains, and scores on the neuropsychiatric inventory (NPI), adjusting for age, sex and education. The table gives the subject characteristics according to study group. Amyloid-negative VCD patients were younger than those who were amyloid-positive. Mean MMSE scores did not differ between study groups. The figure shows the association of VCD diagnosis and amyloid status with neuropsychological test performance. Greatest memory impairment was found in the A+V- group (p<0.05). In VCD patients (V+), co-morbid amyloid-positivity was associated with worse memory performance (A+V+ < A-V+, p<0.05). Conversely, amyloid-negative VCD patients had greater attentional and executive deficits (A-V+ < A+V+, p<0.05), as well as higher NPI scores (A-V+ [15.3±14.0] > A+V+ [9.8±10.5]; p<0.05). The association of VCD diagnosis and amyloid status with neuropsychological test performance.